The FDA is investigating reports of patients developing blood cancer after receiving bluebird bio’s gene therapy Skysona and is evaluating the need for “further regulatory action,” the U.S. agency said last week.
The FDA notification came seven weeks after the New England Journal of Medicine (NEJM) published a report that seven of 67 children who received Skysona during clinical trials had developed blood cancer. The diagnoses had come as early as 14 months after patients received the therapy and as late as 7 years, 8 months after treatment.
Given the risk, providers should consider alternative therapies, including allogenic hematopoietic stem cell transplantation, the FDA said.
“This update from the agency was not prompted by any new cases of malignancy or other safety updates,” a bluebird spokesperson said in an email on Monday. “Hematologic malignancy is a known risk of Skysona and we have been engaged with the FDA on this risk since it was first identified.”
When the FDA approved Skysona in September 2022, it became the most expensive medicine in the world at $3 million for a dose. It is the world’s only therapy for the inherited neurodegenerative disorder cerebral adrenoleukodystrophy (CALD). It has been endorsed for boys ages four through 17 with CALD in its early, active stage.
While citing the blood cancer cases, the NEJM also pointed to the undeniable efficacy of Skysona. In a study of 29 patients six years after treatment, 94% had no neurological decline, with more than 80% remaining free of disability.
When Skysona was approved, its prescribing information included a boxed warning about the risk of developing hematologic cancers. The FDA nod also included a post-marketing requirement for a 15-year follow-up study to evaluate its long-term safety and specifically assess the risk of patients developing secondary malignancies.
The NEJM report said of the seven Skysona patients who developed malignancies, six had myelodysplastic syndrome (MDS) and one had acute myeloid leukemia (AML). There was one death among the MDS patients and another is awaiting treatment. The four others are cancer-free and have not had a recurrence of CALD. The AML patient is alive following a stem cell transplant.
“The wellbeing of patients with CALD treated with Skysona, or who are considering gene therapy following a diagnosis of CALD, is our top priority, and we will continue to follow our established processes to investigate and report potential safety issues,” bluebird's spokesperson said on Monday.
Authors of the NJEM article suggested that the malignancies are related to the lentiviral vector manufacturing process of Skysona. Bluebird’s other gene therapies—Zynteglo for beta thalassemia and Lyfgenia for sickle cell disease—use different lentiviral vectors.
In its third-quarter earnings report last month, bluebird said that five patients had begun therapy this year with Skysona. The company reported revenue of $10.6 million in Q3 and said it expected to generate “at least” $25 million in sales in the fourth quarter.
In September, the company announced a restructuring that reduced its workforce by 25%. The move was designed to reduce bluebird’s operating expenses by about 20% and to help the company break even on quarterly cash flows in the second half of 2025.